The research will evaluate the role of the multiple covalent phosphorylation of liver glycogen synthase in mediating controls of its activity by glucose, insulin, glucagon, catecholamines (both as Alpha-adrenergic and Beta-adrenergic agonists), vasopressin and angiotensin II. Using purified enzymes, we will characterize and map the sites on glycogen synthase phosphorylated by some seven different kinases available to us, including cAMP-dependent protein kinase, two Ca++ dependent protein kinases and four "independent" protein kinases. The effects of such phosphorylations on enzyme activity will be determined. By the use of isolated hepatocytes incubated with 32Pi, antibody techniques for the rapid isolation of glycogen synthase and peptide mapping of the purified protein, we will analyze which phosphorylation sites are phosphorylated in whole cells and which sites are linked to the actions of the above mentioned hormones. This study will provide important information on the possible mechanisms of the hormonal control of hepatic glycogen synthesis.